Single-cell profiling of the copy-number heterogeneity in colorectal cancer

Background:With functionally heterogeneous cells,tumors comprise a complex ecosystem to promote tumor adaptability and evolution under strong selective pressure from the given microenvironment.Diversifying tumor cells or intra-tumor heterogeneity is essential for tumor growth,invasion,and immune evasion.However,no reliable method to classify tumor cell subtypes is yet available.In this study,we introduced the single-cell sequencing combined with copy number characteristics to identify the types of tumor cells in microsatellite stable(MSS)colorectal cancer(CRC).Methods:To characterize the somatic copy number alteration(SCNA)of MSS CRC in a single cell profile,we analyzed 26 tissue samples from 19 Korean patients(GSE132465,the Samsung Medical Center[SMC]dataset)and then verified our findings with 15 tissue samples from five Belgian patients(GSE144735,the Katholieke Universiteit Leuven 3[KUL3]dataset).The Cancer Genome Atlas(TCGA)cohort,GSE39582 cohort,and National Cancer Center(NCC)cohort(24 MSS CRC patients were enrolled in this study between March 2017 and October 2017)were used to validate the clinical features of prognostic signatures.Results:We employed single cell RNA-sequencing data to identify three types of tumor cells in MSS CRC by their SCNA characteristics.Among these three types of tumor cells,C1 and C3 had a higher SCNA burden;C1 had significant chromosome 13 and 20 amplification,whereas C3 was the polar opposite of C1,which exhibited deletion in chromosome 13 and 20.The three types of tumor cells exhibited various functions in the tumor microenvironment and harbored different mutations.C1 and C2 were linked to the immune response and hypoxia,respectively,while C3 was critical for cell adhesion activity and tumor angiogenesis.Additionally,one gene(OLFM4)was identified as epithelium-specific biomarker of better prognosis of CRC(TCGA cohort:P=0.0110;GSE39582 cohort:P=0.0098;NCC cohort:P=0.0360).Conclusions:On the basis of copy number characteristics,we illustrated tumor heterogeneity in MSS CRC and identified three types of tumor cells with distinct roles in tumor microenvironment.By understanding heterogeneity in the intricate tumor microenvironment,we gained an insight into the mechanisms of tumor evolution,which may support the development of therapeutic strategies.

Investigating association between gut microbiota and sarcopenia-related traits:a Mendelian randomization study

Background Observational studies have indicated a potential link between gut microbiota and sarcopenia.However,the underlying mechanisms and a causal relationship have not been established.Thus,the objective of this study is to examine the possible causal association between gut microbiota and sarcopenia-related traits,including low hand-grip strength and appendicular lean mass(ALM),to shed light on the gut–muscle axis.Methods To investigate the potential impact of gut microbiota on low hand-grip strength and ALM,we utilized a two-sample Mendelian randomization(MR)approach.Summary statistics were obtained from genome-wide association studies of gut microbiota,low hand-grip strength,and ALM.The primary MR analysis employed the random-effects inverse-variance weighted(IVW)method.To assess the robustness,we conducted sensitivity analyses using the MR pleiotropy residual sum and outlier(MR-PRESSO)test to detect and correct for horizontal pleiotropy,as well as the MR-Egger intercept test and leave-one-out analysis.Results Alcaligenaceae,Family XIII,and Paraprevotella were positively associated with the risk of low hand-grip strength(P-values<0.05).Streptococcaceae were negatively associated with low hand-grip strength(P-values<0.05).Eight bacterial taxa(Actinomycetales,Actinomycetaceae,Bacteroidaceae,Porphyromonadaceae,Prevotellaceae,Bacteroides,Marvinbryantia,and Phascolarctobacterium)were associated with a higher risk of ALM(P-values<0.05).Eubacterium fissicatena group was negatively associated with ALM(P-values<0.05).Conclusion We found several gut microbiota components causally associated with sarcopenia-related traits.Our findings provided insights into novel strategies for the prevention and treatment of sarcopenia through the regulation of the gut microbiota,contributing to a better understanding of the gut–muscle axis.

斜扩散过程的构造、性质及其应用

斜扩散过程是一类特殊的扩散过程,它所满足的随机微分方程中含有局部时项.由于这类过程具有特殊的路径性质,使得它在物理和生物等领域有着广泛的应用.本文先从斜Brown运动出发,概括总结了斜Brown运动的两种构造方式、离散逼近形式和联合概率分布.在斜Brown运动的基础上,本文给出斜Ornstein-Uhlenbeck (OU)过程和斜分支过程的定义,并展示了它们的诸如转移密度、首达时分布等概率性质.最后介绍了斜扩散过程的一些应用.

Incorporating element doping and quantum dot embedding effects to enhance the thermoelectric properties of higher manganese silicides

Element doping and nano-inclusion embedding are effective approaches to enhance the electrical conductivities and decrease the lattice thermal conductivities of thermoelectric(TE)materials,respectively.However,the intrinsic low electrical thermal conductivities and high electrical properties are severely sacrificed,and the final figure of merit(ZT)is usually restricted.In this study,Ag doping and Pt quantum dot(QD)embedding were synchronously achieved via embedding Ag/Pt alloy QDs into the higher manganese silicides to avoid the conventional single-element doping strategy.The power factor(at 823 K)was enhanced from 1.57×10^(-3) W m^(-1) K^(-2) to 1.82×10^(-3) W m^(-1) K^(-2)(-16%)due to the-18%increase in carrier concentration that was derived from the Ag doping effect.Simultaneously,the lattice thermal conductivity(at 823 K)decreased from 2.65 W m^(-1) K^(-1) e1.92 W m^(-1) K^(-1)(-28%)because of the broadband phonon scattering effect that resulted from the residual Pt QDs inclusions.Synthetically,the optimal ZT value increased by-52%from 0.42 to 0.64 at 823 K.This study demonstrated that incorporating metastable alloy QDs to obtain element doping and nano-inclusion embedding effects is a novel and feasible means to enhance the ZT value of HMS.This method is also possibly applicable to other alloy QD/TE composites.